Abstract: The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.

Abstract: Described herein are Siglec ligand-antibody conjugates and compositions thereof that are useful for suppressing unwanted immune responses such as allergies and anaphylaxis.

Abstract: Disclosed are anti-C3d antibodies or fragments thereof. Also disclosed are methods of killing cancer cells, methods of preparing anti-C3d antibodies, and pharmaceutical compositions.

Abstract: Disclosed herein are methods for identifying proteins as targets for interaction with a small molecule ligand. Also disclosed herein are small molecule ligands and compositions for use in profiling druggable proteins.

Abstract: This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from post-traumatic stress disorder comprising administering a disclosed compound or composition.

Abstract: The invention provides 20-nor-salvinorin A, an analog of the kappa-opioid agonist salvinorin A. The 20-nor-salvinorin A is an active kappa-opioid modulator and can be used for treatment of medical conditions wherein modulation of the kappa-opioid receptor is medically indicated, such as pain, pruritis, depression, or inflammation, or conditions implicating perception and consciousness. 20-nor-salvinorin A can be less additive when used in treatment compared to a mu-opioid receptor agonist, and 20-nor-salvinorin A is more stable in vivo than is parent compound salvinorin A. The invention further provides synthetic intermediates and procedures for preparation of 20-nor-salvinorin A.

Abstract: Provided herein are compounds, compositions and method of using thereof to treat or prevent malaria.

Abstract: Diesters of 4?-ethynyl-2-fluoro-2?-deoxyadenosine and aqueous parenteral suspensions thereof provide extended in vivo viral suppression of human immunodeficiency virus (HIV).

Abstract: Provided herein are compounds, compositions and methods of using thereof for treatment and/or prevention infections of viruses such as HIV and HBV by administering a certain esters and other derivatives of 4?-ethynyl-2-fluoro-2?-deoxyadenosine (EFdA) or a pharmaceutically acceptable salt thereof.

Abstract: A recombinantly expressed nucleotide triphosphate transporter efficiently imports the triphosphates of unnatural nucleotides into cells, and the endogenous cellular machinery incorporates those nucleotides into cellular nucleic acids. UBPs can therefore form within the cell's nucleic acids. Moreover, neither the presence of the unnatural triphosphates nor the replication of the UBP represents a significant growth burden. The UBP is not efficiently excised by nucleic acid repair pathways, and therefore can be retained as long as the unnatural triphosphates are available in the growth medium. Thus, the resulting cell is the first organism to stably propagate an expanded genetic alphabet.

Abstract: Disclosed herein are chimeric polypeptides, including compositions thereof, expression vectors, and methods of use thereof, for the generation of transgenic cells, tissues, plants, and animals. The compositions, vectors, and methods of the present invention are also useful in gene therapy techniques.

Abstract: Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X1—S(O)(X2)F)m groups attached thereto, wherein Z is O, NR, or N; X1 is a covalent bond or CH2CH2; m can be 1 or 2 depending on the identity of Z; and X2 is O or NR. In some embodiments, the core group is an amino acid or a protein. In some embodiments the core group is a compound that has therapeutic activity toward a therapeutic target.

Abstract: The present invention provides novel scaffolded HIV-1 vaccine immunogens. Some of the scaffolded immunogens contain a soluble gp140 trimer linked to the N-terminus of the nanoparticle subunit and a T-helper epitope that is fused via a short peptide spacer to the C-terminus of the nanoparticle subunit. Some other immunogens of the invention contain a soluble gp140 trimer protein that is linked to a stable nanoparticle via a short peptide spacer that is a T-helper epitope. Some of the scaffolded immunogens contain a gp140 trimer immunogen presented on a nanoparticle platform formed with I3-01 protein, E2p, or variants of protein 1VLW. Also provided in the invention are nucleic acids that encode the various vaccine immunogens described herein, and expression vectors and host cells harboring the nucleic acids. The invention further provides methods of using the scaffolded HIV-1 vaccine immunogens for preventing or treating HIV infections.

Abstract: Disclosed herein are compounds, their pharmaceutical salts, and pharmaceutical compositions that selectively activate the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1s) signaling pathway of the unfolded protein response (UPR), but that do not target the IRE1 kinase domain. The compounds are useful in treating diseases or conditions characterized by imbalances in proteostasis within the endoplasmic reticulum (ER) or secretory pathway, including those not associated with ER stress or activation of UPR.

Abstract: Disclosed herein are compounds, compositions, and methods of their use for the treatment of diabetes.

Abstract: Disclosed herein are immunoglobulin fusion proteins comprising an insulin therapeutic peptide and an immunoglobulin region that targets the insulin therapeutic peptide to the liver of an individual in need thereof. Further disclosed herein are compositions comprising the immunoglobulin fusion proteins and methods for using the immunoglobulin fusion proteins for the treatment or prevention of a disease or condition in a subject, for example, diabetes and diabetes related conditions.

Abstract: The invention provides compositions and methods for disrupting preformed bacterial biofilm or preventing formation of bacterial biofilm. Also provided in the invention are methods and compositions for treating and preventing chronic rhinosinusitis. Such compositions and methods utilize one or more antibiotic compounds in combination with at least one phospholipid compound described herein.

Abstract: The present invention relates to antibodies against influenza neuraminidase, compositions containing the antibodies and methods of using the antibodies.

Abstract: Disclosed herein are immunoglobulin constructs comprising at least one immunoglobulin domain or fragment thereof; and a therapeutic polypeptide or derivative or variant thereof attached to or inserted into said immunoglobulin domain. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a knob domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said knob domain of the CDR3H. Also provided are immunoglobulin constructs comprising a mammalian immunoglobulin heavy chain comprising at least a portion of a stalk domain in the complementarity-determining region 3 (CDR3H) or fragment thereof; and a therapeutic polypeptide attached to or inserted into said stalk domain of the CDR3H. Also described herein are methods and compositions comprising the immunoglobulin constructs described herein for treatment and prevention of a disease or condition in a subject.

Abstract: Systems and method for sorting droplets includes a microfluidic chip or substrate having a droplet sorting channel coupled at an upstream location to a droplet inlet channel, the droplet sorting channel coupled at a downstream location to a waste channel and a collection channel. The device includes an optical interrogation device configured to illuminate the droplets passing through the sorting channel with excitation light from an excitation light source and capturing emitted fluorescent light and generating an output signal correlated to the fluorescence of the droplets. An actuator (electrode) is disposed in the microfluidic chip or substrate and coupled to a signal driver (e.g., a high voltage amplifier). The device or system uses a programmable controller configured to receive the output signals from the optical interrogation device and trigger the signal driver to actuate the actuator to direct the droplets into the collection channel.